Conservation of inner nuclear membrane targeting sequences in mammalian Pom121 and yeast Heh2 membrane proteins
Basheer, Noorjahan Jagalur
Van Den Boom, Vincent
Lokareddy, Ravi K.
Veenhoff, Liesbeth M.
AffiliationUniversity of Groningen
Erasmus Medical Center/Sophia Children’s Hospital
Thomas Jefferson University
Subjectsnuclear membrane targeting sequences
Subject Categories::C700 Molecular Biology, Biophysics and Biochemistry
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AbstractEndoplasmic reticulum-synthesized membrane proteins traffic through the nuclear pore complex (NPC) en route to the inner nuclear membrane (INM). Although many membrane proteins pass the NPC by simple diffusion, two yeast proteins, ScSrc1/ScHeh1 and ScHeh2, are actively imported. In these proteins, a nuclear localization signal (NLS) and an intrinsically disordered linker encode the sorting signal for recruiting the transport factors for FG-Nup and RanGTP-dependent transport through the NPC. Here we address whether a similar import mechanism applies in metazoans. We show that the (putative) NLSs of metazoan HsSun2, MmLem2, HsLBR, and HsLap2β are not sufficient to drive nuclear accumulation of a membrane protein in yeast, but the NLS from RnPom121 is. This NLS of Pom121 adapts a similar fold as the NLS of Heh2 when transport factor bound and rescues the subcellular localization and synthetic sickness of Heh2ΔNLS mutants. Consistent with the conservation of these NLSs, the NLS and linker of Heh2 support INM localization in HEK293T cells. The conserved features of the NLSs of ScHeh1, ScHeh2, and RnPom121 and the effective sorting of Heh2-derived reporters in human cells suggest that active import is conserved but confined to a small subset of INM proteins.
CitationKralt A, Basheer NJ, Van Den Boom V, Lokareddy R, Steen A, Cingolani G, Fornerod M, Veenhoff L (2015) 'Conservation of inner nuclear membrane targeting sequences in mammalian Pom121 and yeast Heh2 membrane proteins', Molecular Biology of the Cell, 26 (18), pp.3301-3312.
PublisherAmerican Society for Cell Biology
JournalMolecular Biology of the Cell
PubMed Central IDPMC4569319
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